anastrozole in preventing breast cancer in postmenopausal women at increased risk of breast cancer

Conditions: Breast Cancer

Summary: rationale: chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. anastrozole may be effective in preventing breast cancer. purpose: this randomized clinical trial is studying how well anastrozole works in preventing breast cancer in postmenopausal women who are at increased risk for the disease.

objectives: primary * determine the effectiveness of anastrozole in preventing breast cancer in postmenopausal women at increased risk for the disease. secondary * determine the role of this drug in preventing estrogen receptor-positive breast cancer in these participants. * determine the effect of this drug on breast cancer mortality in these participants. * determine the effect of this drug on other cancers, cardiovascular disease, fracture rates, and non-breast cancer deaths in these participants. * determine the tolerability and acceptability of side effects of this drug in these participants. outline: this is a randomized, double-blind, placebo-controlled, multicenter study. participants are stratified according to participating center. participants are randomized to 1 of 2 treatment arms. * arm i: participants receive oral anastrozole daily for 5 years. * arm ii: participants receive an oral placebo daily for 5 years. in both arms, treatment continues in the absence of the development of breast cancer (including ductal carcinoma in situ), a drop in the t-score below minus 4, or the occurrence of a new fragility fracture. participants are followed for at least a further 5 years. peer reviewed and funded or endorsed by cancer research uk accrual: a total of 3,864 participants were recruited for this study over 10 years.

Eligibility criteria:
disease characteristics: * meets at least 1 of the relative risk factors based on age as follows: * 45 to 70 years of age: * first-degree relative who developed breast cancer at ≤ 50 years of age * first-degree relative who developed bilateral breast cancer * two or more first- or second-degree relatives who developed breast cancer or ovarian cancer * participants having both relatives who are second degree and on the opposite sides of the family must have at least one that was diagnosed at ≤ 50 years of age * nulliparous (or first birth at ≥ 30 years of age) and a first-degree relative who developed breast cancer * benign biopsy with proliferative disease and a first-degree relative who developed breast cancer * mammographic opacity covering at least 50% of the breast in the absence of hormone replacement therapy within the past 3 months * 60 to 70 years of age: * first-degree relative with breast cancer at any age * age at menopause ≥ 55 years * nulliparous or age at first birth ≥ 30 years * 40 to 44 years of age: * two or more first- or second-degree relatives who developed breast cancer or ovarian cancer at ≤ 50 years of age * first-degree relative with bilateral breast cancer who developed the first breast cancer at ≤ 50 years of age * nulliparous (or first birth at ≥ 30 years of age) and a first-degree relative who developed breast cancer at ≤ 40 years of age * benign biopsy with proliferative disease and a first-degree relative who developed breast cancer at ≤ 40 years of age * all age groups (40 to 70 ears of age) with a 10-year risk \> 5% who do not fit into the above categories are allowed * clearly apparent family history and/or other risk factors indicating appropriate increased risk of breast cancer for age * the following prior breast conditions are allowed (for all age groups): * lobular carcinoma in situ * atypical ductal or lobular hyperplasia in a benign lesion * ductal carcinoma in-situ (dcis), diagnosed within the past 6 months, and treated by mastectomy * no evidence of breast cancer on mammogram within the past year * hormone receptor status: * for patients with prior dcis, estrogen- or progesterone-receptor status must have been positive * must have had greater than or equal to 5% positive cells patient characteristics: age * 40 to 70 sex * female menopausal status * postmenopausal, defined as at least 1 of the following: * over 60 years of age * bilateral oophorectomy * ≤ 60 years of age with a uterus and amenorrhea for at least 12 months * ≤ 60 years of age without a uterus and with follicle-stimulating hormone levels \> 30 iu/l performance status * not specified life expectancy * at least 10 years hematopoietic * not specified hepatic * not specified renal * not specified other * psychologically and physically suitable to receive 5 years of anti-estrogen therapy * no cancer within the past 5 years except non-melanoma skin cancer or carcinoma in situ of the cervix * no evidence of osteoporosis or fragility fractures within the spine * participants with a t-score \> minus 4 and no more than 2 fragility fractures are allowed * no concurrent severe disease that would place the participant at unusual risk or confound the results of the study * no other medical condition that would preclude the ability to receive the study treatment prior concurrent therapy: biologic therapy * not specified chemotherapy * not specified endocrine therapy * no prior tamoxifen, raloxifene, or other selective estrogen receptor modulator (serm) use for more than 6 months in duration unless an ibis-i participant (must have been off trial therapy for at least 5 years. * no concurrent tamoxifen, raloxifene, or other serm * no concurrent estrogen-based hormone replacement therapy * no concurrent systemic estrogen replacement therapy, including vaginal estrogen preparations radiotherapy * not specified surgery * see disease characteristics * no prior prophylactic mastectomy * no concurrent prophylactic mastectomy other * more than 6 months since prior investigational drugs

Keywords: breast cancer, chemoprevention